Phosphatase Subfamily DSP1 - Revision history

Gerard at 15:19, 22 March 2017

2017-03-22T15:19:14Z

Gerard at 15:12, 22 March 2017

2017-03-22T15:12:59Z

Gerard at 15:11, 22 March 2017

2017-03-22T15:11:48Z

Mark at 20:14, 11 November 2015

2015-11-11T20:14:25Z

Mark: /* References */

2015-07-01T21:03:53Z

‎References

Mark: /* DUSP1 (MKP1/hVH1) */

2015-07-01T21:03:28Z

‎DUSP1 (MKP1/hVH1)

Mark: /* Domain Structure */

2015-06-25T04:27:50Z

‎Domain Structure

Mark: /* Domain Structure */

2015-06-25T04:27:35Z

‎Domain Structure

Mark at 18:04, 15 June 2015

2015-06-15T18:04:20Z

Mark at 16:11, 29 May 2015

2015-05-29T16:11:34Z

← Older revision		Revision as of 15:19, 22 March 2017
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	(Note: It is worthy pointing out that DUSP1 expression is strictly regulated at low level in brain (see [http://www.gtexportal.org/home/gene/DUSP1 GTEx])).		(Note: It is worthy pointing out that DUSP1 expression is strictly regulated at low level in brain (see [http://www.gtexportal.org/home/gene/DUSP1 GTEx])).
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−	~~(PS: more reading is needed).~~

	====== DUSP2 (PAC1) ======		====== DUSP2 (PAC1) ======

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 [[Phosphatase classification|Phosphatase Classification]]:  Superfamily [[Phosphatase_Superfamily_CC1|CC1]]: Family [[Phosphatase_Family_DSP|DSP]]: [[Phosphatase_Subfamily_DSP1|Subfamily DSP1]]
-DSP1 is inducible nuclear MKPs conserved throughout eukaryotes. As a key player in MAPK pathway, it is implicated in immune regulation and cancer.
+DSP1 is an inducible nuclear MAP Kinase phosphatase (MKP) conserved throughout eukaryotes. As a key player in MAPK pathway, it is implicated in immune regulation and cancer.
 ===Evolution===
-DSP1 subfamily is widely found across eukaryotes. It is present in animals, plants, amoeba, and some basal eukaryotes, but is absent from ecdysozoa (nematodes and arthropods), most fungi and monosiga (unpublished data, [http://resdev.gene.com/gOrtholog/view/cluster/MC0008107/overview DUSP1], [http://resdev.gene.com/gOrtholog/view/cluster/MC0013833/overview DUSP2], [http://resdev.gene.com/gOrtholog/view/cluster/MC0006670/overview DUSP4], [http://resdev.gene.com/gOrtholog/view/cluster/MC0008873/overview DUSP5]).
+DSP1 subfamily is widely found across eukaryotes. It is present in animals, plants, amoeba, and some basal eukaryotes, but is absent from ecdysozoa (nematodes and arthropods), most fungi and Monosiga (unpublished data, [http://resdev.gene.com/gOrtholog/view/cluster/MC0008107/overview DUSP1], [http://resdev.gene.com/gOrtholog/view/cluster/MC0013833/overview DUSP2], [http://resdev.gene.com/gOrtholog/view/cluster/MC0006670/overview DUSP4], [http://resdev.gene.com/gOrtholog/view/cluster/MC0008873/overview DUSP5]).
 ===Domain Structure===
-DSP1 has an inactive rhodanese domain, followed by a phosphatase domain. In general, a kinase interaction motif (KIM) embedded in rhodanese domain mediates the interaction between DSP1 and MAPK (i.e. ERK, JNK, p38 kinase subfamilies) <cite>Mandl05, Farooq03, Zhang05, Kucharska09</cite>. (Note: compare the complex structure.)
+DSP1 has an inactive rhodanese domain, followed by a phosphatase domain. In general, a kinase interaction motif (KIM) embedded in rhodanese domain mediates the interaction between DSP1 and MAPK (i.e. ERK, JNK, p38 kinase subfamilies) <cite>Mandl05, Farooq03, Zhang05, Kucharska09</cite>.
 Dictyostelium has four DSP1s. Two (mkpB-1 and mkpB-2) have the typical domain combination of rhodanese domain and phosphatase domain. Another two have different domain combination. Both of them have a long N-terminal region. One of the two, mkpA, has three weak hits to [[Protein_Domain#Gelsolin|Gelsolin domain]], an actin-binding protein that is a key regulator of actin filament assembly and disassembly.

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 [[Phosphatase classification|Phosphatase Classification]]:  Superfamily [[Phosphatase_Superfamily_CC1|CC1]]: Family [[Phosphatase_Family_DSP|DSP]]: [[Phosphatase_Subfamily_DSP1|Subfamily DSP1]]
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 DSP1 has an inactive rhodanese domain, followed by a phosphatase domain. In general, a kinase interaction motif (KIM) embedded in rhodanese domain mediates the interaction between DSP1 and MAPK (i.e. ERK, JNK, p38 kinase subfamilies) <cite>Mandl05, Farooq03, Zhang05, Kucharska09</cite>. (Note: compare the complex structure.)
-Dictystelium has four DSP1s. Two (mkpB-1 and mkpB-2) have the typical domain combination of rhodanese domain and phosphatase domain. Another two have different domain combination. Both of them have a long N-terminal region. One of the two, mkpA, has three weak hits to [[Protein_Domain#Gelsolin|Gelsolin domain]], an actin-binding protein that is a key regulator of actin filament assembly and disassembly.
+Dictyostelium has four DSP1s. Two (mkpB-1 and mkpB-2) have the typical domain combination of rhodanese domain and phosphatase domain. Another two have different domain combination. Both of them have a long N-terminal region. One of the two, mkpA, has three weak hits to [[Protein_Domain#Gelsolin|Gelsolin domain]], an actin-binding protein that is a key regulator of actin filament assembly and disassembly.
 ===Functions===

← Older revision		Revision as of 20:14, 11 November 2015
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−	~~__NOTOC__~~
	[[Phosphatase classification\|Phosphatase Classification]]: Superfamily [[Phosphatase_Superfamily_CC1\|CC1]]: Family [[Phosphatase_Family_DSP\|DSP]]: [[Phosphatase_Subfamily_DSP1\|Subfamily DSP1]]		[[Phosphatase classification\|Phosphatase Classification]]: Superfamily [[Phosphatase_Superfamily_CC1\|CC1]]: Family [[Phosphatase_Family_DSP\|DSP]]: [[Phosphatase_Subfamily_DSP1\|Subfamily DSP1]]

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 #Patterson09 pmid=19228121
 #Peng10 pmid=21084841
 #Shin13 pmid=23402999
 #Smallie15 pmid=26019272

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 ====== DUSP1 (MKP1/hVH1) ======
 DUSP1 is the best characterized phosphatase within this subfamily. It prefers to dephosphorylates p38 and JNK over ERK. DUSP1 is involved in immune regulation and cancer. DUSP1 is an important negative-feedback regulator of macrophage function (possibly by modulating mRNA-destabilizing protein tristetraprolin <cite> Smallie15</cite>) and the inflammatory response to TLR signalling, and plays key regulatory roles in both innate and adaptive immune responses via inactivation of p38 and JNK (reviewed in <cite>Patterson09</cite>).  DUSP1 is an important negative regulator of pro-allergic responses in airway epithelium <cite>Golebski15</cite>.
 (Note: It is worthy pointing out that DUSP1 expression is strictly regulated at low level in brain (see [http://www.gtexportal.org/home/gene/DUSP1 GTEx])).

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 ====== DUSP5 (hVH3) ======
-DUSP5 is an inducible nuclear ERK-specific MKP that functions as both an inactivator of and a nuclear anchor for ERK2 in mammalian cells <cite>Ishibashi94, Mandl05</cite>. Thus, it modules T-cell development and function <cite>Kovanen08</cite>, modules corneal epithelial cell proliferation <cite>Wang10</cite>, is implicated in angiogenesis <cite>Echavarria13</cite>, and influences myeloid cell fate by [http://www.frontiersin.org/files/Articles/80339/fimmu-05-00048-HTML/image_m/fimmu-05-00048-g001.jpg M-CSF pathway] <cite>Grasset10</cite>. It may be involved in carcinogenesis, since DUSP5 is down-regulated in gastric cancer by promoter CpG island hypermethylation <cite>Shin13</cite> and up-regulated in [http://en.wikipedia.org/wiki/MCF-7 MCF-7 human breast carcinoma cells] by transcription factor [http://en.wikipedia.org/wiki/C-jun c-Jun] <cite>Nunes-Xavier10</cite>.
+DUSP5 is an inducible nuclear ERK-specific MKP that functions as both an inactivator of and a nuclear anchor for ERK2 in mammalian cells <cite>Ishibashi94, Mandl05</cite>. Thus, it modules T-cell development and function <cite>Kovanen08</cite>, modules corneal epithelial cell proliferation <cite>Wang10</cite>, is implicated in angiogenesis <cite>Echavarria13</cite>, and influences myeloid cell fate by [http://www.frontiersin.org/files/Articles/80339/fimmu-05-00048-HTML/image_m/fimmu-05-00048-g001.jpg M-CSF pathway] <cite>Grasset10</cite>. It may be involved in carcinogenesis, since DUSP5 is down-regulated in gastric cancer by promoter CpG island hypermethylation <cite>Shin13</cite>, up-regulated in [http://en.wikipedia.org/wiki/MCF-7 MCF-7 human breast carcinoma cells] by transcription factor [http://en.wikipedia.org/wiki/C-jun c-Jun] <cite>Nunes-Xavier10</cite> and its down-regulation predicts poor prognosis of patients with prostate cancer <cite>Cai15</cite>.
 Similar with DUSP4, DUSP5 is also stabilized by binding to and be phosphorylated by ERK. The accumulation of DUSP5 protein is regulated by rapid proteasomal degradation. DUSP5 is phosphorylated by ERK1/2 both in vitro and in vivo on three sites (Thr321, Ser346 and Ser376) at C-terminus. Co-expression of ERK2 results in significant stabilisation of DUSP5, which is accompanied by reduced levels of DUSP5 ubiquitination. However, there is no evidence that phosphorylation of DUSP5 by ERK2 significantly affects either the half-life of the DUSP5 protein or its ability to bind to, inactivate or anchor ERK2 in the nucleus. These changes are independent of ERK2 kinase activity but absolutely depend on the ability of ERK2 to bind to DUSP5 <cite>Kucharska09</cite>.
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 #Cadalbert05 pmid=16038800
 #Cadalbert10 pmid=19843478
 #Chen01 pmid=11387337
 #Chu96 pmid=8626452